ORCID Profile
0000-0002-3405-5769
Current Organisation
University of Nottingham
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Publisher: Wiley
Date: 30-03-2007
DOI: 10.1111/J.1748-1716.2007.01698.X
Abstract: Membrane fatty acid transporters can modulate the balance between fatty acid uptake and subsequent storage and/or oxidation in muscle tissue. As such, skeletal muscle fatty acid transporter protein expression could play an important role in the etiology of insulin resistance and/or type 2 diabetes. In the present study, fatty acid translocase (FAT/CD36), plasma membrane-bound fatty acid-binding protein (FABPpm) and fatty acid transport protein 1 (FATP1) mRNA and protein expression were assessed in muscle tissue obtained from 10 sedentary, overweight type 2 diabetes patients (60 +/- 2 years), 10 sedentary, weight-matched normoglycemic controls (60 +/- 2 years) and 10 age-matched, endurance trained cyclists (57 +/- 1 years). Both FAT/CD36 and FATP1 mRNA and protein expression did not differ between groups. In contrast, FABPpm mRNA and protein expression were approx. 30-40% higher in the trained men compared with the diabetes patients (P < 0.01) and sedentary controls (P < 0.05). Skeletal muscle FAT/CD36, FABPpm and FATP1 mRNA and protein expression are not up- or downregulated in a sedentary and/or insulin resistant state. In contrast, FABPpm expression is upregulated in the endurance trained state and likely instrumental to allow greater fatty acid oxidation rates.
Publisher: eLife Sciences Publications, Ltd
Date: 16-04-2018
DOI: 10.7554/ELIFE.34114
Abstract: Circadian regulation of transcriptional processes has a broad impact on cell metabolism. Here, we compared the diurnal transcriptome of human skeletal muscle conducted on serial muscle biopsies in vivo with profiles of human skeletal myotubes synchronized in vitro. More extensive rhythmic transcription was observed in human skeletal muscle compared to in vitro cell culture as a large part of the in vivo mRNA rhythmicity was lost in vitro. siRNA-mediated clock disruption in primary myotubes significantly affected the expression of ~8% of all genes, with impact on glucose homeostasis and lipid metabolism. Genes involved in GLUT4 expression, translocation and recycling were negatively affected, whereas lipid metabolic genes were altered to promote activation of lipid utilization. Moreover, basal and insulin-stimulated glucose uptake were significantly reduced upon CLOCK depletion. Our findings suggest an essential role for the circadian coordination of skeletal muscle glucose homeostasis and lipid metabolism in humans.
Publisher: American Physiological Society
Date: 03-2020
DOI: 10.1152/AJPENDO.00344.2019
Abstract: Muscle anabolic resistance to dietary protein is associated with obesity and insulin resistance. However, the contribution of excess consumption of fat to anabolic resistance is not well studied. The aim of these studies was to test the hypothesis that acute and short-term dietary fat overload will impair the skeletal muscle protein synthetic response to dietary protein ingestion. Eight overweight/obese men [46.4 ± 1.4 yr, body mass index (BMI) 32.3 ± 5.4 kg/m 2 ] participated in the acute feeding study, which consisted of two randomized crossover trials. On each occasion, subjects ingested an oral meal (with and without fat emulsion), 4 h before the coingestion of milk protein, intrinsically labeled with [1- 13 C]phenylalanine, and dextrose. Nine overweight/obese men (44.0 ± 1.7 yr, BMI 30.1 ± 1.1 kg/m 2 ) participated in the chronic study, which consisted of a baseline, 1-wk isocaloric diet, followed by a 2-wk high-fat diet (+25% energy excess). Acutely, incorporation of dietary amino acids into the skeletal muscle was twofold higher ( P 0.05) in the lipid trial compared with control. There was no effect of prior lipid ingestion on indices of insulin sensitivity (muscle glucose uptake, pyruvate dehydrogenase complex activity, and Akt phosphorylation) in response to the protein/dextrose drink. Fat overfeeding had no effect on muscle protein synthesis or glucose disposal in response to whey protein ingestion, despite increased muscle diacylglycerol C16:0 ( P = 0.06) and ceramide C16:0 ( P 0.01) levels. Neither acute nor short-term dietary fat overload has a detrimental effect on the skeletal muscle protein synthetic response to dietary protein ingestion in overweight/obese men, suggesting that dietary-induced accumulation of intramuscular lipids per se is not associated with anabolic resistance.
Publisher: American Diabetes Association
Date: 18-12-2014
DOI: 10.2337/DB14-0961
Abstract: The ability to maintain skeletal muscle mass appears to be impaired in insulin-resistant conditions, such as type 2 diabetes, that are characterized by muscle lipid accumulation. The current study investigated the effect of acutely increasing lipid availability on muscle protein synthesis. Seven healthy young male volunteers underwent a 7-h intravenous infusion of l-[ring-2H5]phenylalanine on two randomized occasions combined with 0.9% saline or 10% Intralipid at 100 mL/h. After a 4-h “basal” period, a 21-g bolus of amino acids was administered and a 3-h hyperinsulinemic-euglycemic cl was commenced (“fed” period). Muscle biopsy specimens were obtained from the vastus lateralis at 1.5, 4, and 7 h. Lipid infusion reduced fed whole-body glucose disposal by 20%. Furthermore, whereas the mixed muscle fractional synthetic rate increased from the basal to the fed period during saline infusion by 2.2-fold, no change occurred during lipid infusion, despite similar circulating insulin and leucine concentrations. This “anabolic resistance” to insulin and amino acids with lipid infusion was associated with a complete suppression of muscle 4E-BP1 phosphorylation. We propose that increased muscle lipid availability may contribute to anabolic resistance in insulin-resistant conditions by impairing translation initiation.
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.EXGER.2017.03.018
Abstract: The aim of this study was to examine the temporal relationship between intramyocellular lipid (IMCL) content and the expression of genes associated with IMCL turnover, fat metabolism, and inflammation during recovery from an acute bout of resistance type exercise in old versus young men. Seven healthy young (23±2years, 77.2±2.9kg) and seven healthy older (72±1years, 79.3±4.9kg) males performed a single bout of resistance exercise involving 6 sets of 10 repetitions of leg press and 6 sets of 10 repetitions of leg extension at 75% one-repetition maximum (1-RM). Muscle biopsy s les were obtained before and 12, 24 and 48h after the completion of exercise and analysed for IMCL content and the expression of 48 genes. The subjects refrained from further heavy physical exercise and consumed a standardized diet for the entire experimental period. The IMCL content was ~2-fold higher at baseline and 12h post-exercise in old compared with young in iduals. However, no differences between groups were apparent after 48h of recovery. There was higher expression of genes involved in fatty acid synthesis (FASN and PPARγ) during the first 24h of recovery. Differential responses to exercise were observed between groups for a number of genes indicating increased inflammatory response (IL6, IkBalpha, CREB1) and impaired fat metabolism and TCA cycle (LPL, ACAT1, SUCLG1) in older compared with younger in iduals. A singe bout of resistance type exercise leads to molecular changes in skeletal muscle favouring reduced lipid oxidation, increased lipogenesis, and exaggerated inflammation during post-exercise recovery in the older compared with younger in iduals, which may be indicative of a blunted response of IMCL turnover with ageing.
Publisher: The Endocrine Society
Date: 2007
DOI: 10.1210/JC.2006-1592
Abstract: Aim: The aim of this report was to study the effect of high-fat (HF)/low-carbohydrate (CHO) diet on regulation of substrate metabolism in humans. Methods: Ten healthy men consumed either a HF (75% energy as fat) or control (35%) diet for 6 d in random order. On d 7, blood glucose disappearance rate (Rd) was determined before and during a hyperinsulinemic euglycemic cl . Substrate oxidation was determined by indirect calorimetry. Muscle biopsies were obtained prediet, postdiet, and postcl s. Results: Rd was similar under basal conditions but slightly elevated (∼10%, P & 0.05) during the last 30 min of the cl after the HF diet. HF diet reduced CHO oxidation under basal (by ∼40%, P & 0.05) and cl conditions (by ∼20%, P & 0.05), increased insulin-mediated whole-body nonoxidative glucose disposal (by 30%, P & 0.05) and muscle glycogen storage (by ∼25%, P & 0.05). Muscle pyruvate dehydrogenase complex activity was blunted under basal and cl conditions after HF compared with control (P & 0.05) and was accompanied by an approximately 2-fold increase (P & 0.05) in pyruvate dehydrogenase kinase 4 (PDK4) mRNA and protein expression. Conclusion: Short-term HF/low-CHO dietary intake did not induce whole-body insulin resistance, but caused a shift in im glucose metabolism from oxidation to glycogen storage. Insulin-stimulated CHO oxidation and muscle pyruvate dehydrogenase complex activity were blunted after the HF diet. Up-regulation of muscle PDK4 expression was an early molecular adaptation to these changes, and we showed for the first time in healthy humans, unlike insulin-resistant in iduals, that insulin can suppress PDK4 but not PDK2 gene expression in skeletal muscle.
Publisher: Springer Science and Business Media LLC
Date: 02-02-2018
Publisher: Springer Science and Business Media LLC
Date: 06-10-2023
Publisher: The Endocrine Society
Date: 03-2008
DOI: 10.1210/JC.2007-1981
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Kostas Tsintzas.